TCTN2 (Tectonic-2, Q96GX1) review notes

Deep research status

• just deep-research-falcon human TCTN2 was run first with --fallback perplexity-lite (default 600 s timeout; perplexity-lite is not available in this environment), then rerun with --timeout 2400. See the bottom of this file for the outcome. The review below rests on the cached primary literature in publications/.

Protein

• Single-pass type I membrane protein: signal peptide 1-25, large luminal/extracellular tectonic domain (26-668), TM 669-689, short cytoplasmic tail (UniProt).
• Tectonic family (TCTN1-3). MKS8 and JBTS24 disease gene PMID:21462283.

Complex membership and location

• Part of the Tctn1/MKS transition-zone complex PMID:21725307.
• Co-purifies with Tmem231 PMID:25869670.
• In the TZ, near the ciliary membrane PMID:29866362.

Function

• Required for ciliogenesis in mouse (tissue-dependent) PMID:21565611. But some null MEFs ciliate PMID:28401750.
• Tissue-specific defects in ciliogenesis and ciliary membrane composition PMID:21725307.
• Human RPE1 TCTN2 KO PMID:29866362. MKS module assembly PMID:29866362.
• Hedgehog signalling PMID:21565611. This is indirect, via ciliary gating.

Curation decisions

• TZ, MKS complex, cilium assembly, protein localization to TZ: ACCEPT (core).
• Smoothened signalling (IBA/IEA/ISS): KEEP_AS_NON_CORE (downstream of the gate).
• Ciliary membrane (Reactome TAS): ACCEPT (the TZ membrane is a ciliary membrane domain; TCTN2 TM segment sits there).
• NEW: GO:1905349 ciliary transition zone assembly (IMP, PMID:29866362). TCTN2 is a structural TZ constituent needed to incorporate TMEM67/MKS1 (scaffold case). GO:1905349 replaces the obsoleted GO:0097711 and has only ~9 human/mouse annotations (CEP290, CCDC66, DZIP1L, RAB3IP; QuickGO query 2026-10), so the absence for MKS subunits is a sparse-term gap rather than a convention.

HPA cilium atlas vs module role

• HPA (member_evidence.md): TCTN2 "Primary cilium transition zone (A)" (Approved); HPA main locations Golgi apparatus; Microtubules. The Hansen et al. 2025 atlas PMID:41005307 thus places TCTN2 at the TZ with an Approved grade. It is one of the few MKS-module members whose HPA call names the TZ sub-compartment specifically.
• Module role: MKS module component (ciliary diffusion barrier; process ciliary transition zone assembly; location ciliary transition zone). The HPA call agrees with the module role and with the literature. The Golgi pool is expected for a glycosylated single-pass membrane protein in transit. GOA has no HPA (GO_REF:0000052) row for TCTN2; the TZ IDA from HPA could be added by GOA.
• core_functions agree with the module (MKS complex, TZ, TZ assembly, protein localization to TZ).

Deep research outcome

• Falcon succeeded on the --timeout 2400 rerun (TCTN2-deep-research-falcon.md). Its synthesis (MKS/NPHP-module transition-zone organizer; non-enzymatic; ciliary gate/composition role) matches the conclusions above. No annotation decisions changed after reading it.